Our goal is to elucidate the molecular mechanisms by which the haloethylenes, such as 1,1-dichloroethylene, and trichloroethylene, cause acute liver injury. Our hypothesis is that the toxicity of haloethylenes is a consequence of their biotransformation to reactive species capable of altering cell macromolecules. Haloethylene toxicity and biotransformation can be modulated by pre-treatments which have a variety of effects, including induction of mixed function of oxidase components, particularly cytochrome P-450, or alterations in the availability of glutathione or changes in the intercellular levels of reducing equivalents. We propose use of such pre-treatments to facilitate characterization of the biologic responses and metabolic products involved in the injurious interactions between reactive haloethylene species and cell macromolecules. Acute hepatic injury will be characterized by a multi-faceted chemical, enzymatic and morphologic approach. Haloethylene biotransformation will be monitored in whole animals, in isolated hepatocytes, and in cell fractions, and metabolites including covalently bound macromolecules will be isolated and identified. Relationships will be sought between injury and specific metabolic products. Patterns of metabolite production indicative of injurious metabolic pathways will be sought in animals in order to develop non-invasive methods to screen for haloethylene injury in man.